Functional interplay between the oxidative stress response and DNA damage checkpoint signaling for genome maintenance in aerobic organisms

Ji Eun Choi; Woo-Hyun Chung

doi:10.1007/s12275-020-9520-x

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Functional interplay between the oxidative stress response and DNA damage checkpoint signaling for genome maintenance in aerobic organisms: Ji Eun Choi ^1,2, Woo-Hyun Chung ^1,2; Journal of Microbiology 2020;58(2):81-91.
DOI: https://doi.org/10.1007/s12275-020-9520-x
Published online: December 23, 2019

¹College of Pharmacy, Duksung Women’s University, Seoul 01369, Republic of Korea, ²Innovative Drug Center, Duksung Women’s University, Seoul 01369, Republic of Korea¹College of Pharmacy, Duksung Women’s University, Seoul 01369, Republic of Korea, ²Innovative Drug Center, Duksung Women’s University, Seoul 01369, Republic of Korea

Corresponding author: Woo-Hyun Chung , Tel: +82-2-901-8737,

Received: 4 November 2019 • Revised: 29 November 2019 • Accepted: 30 November 2019

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Abstract

The DNA damage checkpoint signaling pathway is a highly conserved surveillance mechanism that ensures genome integrity by sequential activation of protein kinase cascades. In mammals, the main pathway is orchestrated by two central sensor kinases, ATM and ATR, that are activated in response to DNA damage and DNA replication stress. Patients lacking functional ATM or ATR suffer from ataxia-telangiectasia (A-T) or Seckel syndrome, respectively, with pleiotropic degenerative phenotypes. In addition to DNA strand breaks, ATM and ATR also respond to oxidative DNA damage and reactive oxygen species (ROS), suggesting an unconventional function as regulators of intracellular redox status. Here, we summarize the multiple roles of ATM and ATR, and of their orthologs in Saccharomyces cerevisiae, Tel1 and Mec1, in DNA damage checkpoint signaling and the oxidative stress response, and discuss emerging ideas regarding the possible mechanisms underlying the elaborate crosstalk between those pathways. This review may provide new insights into the integrated cellular strategies responsible for maintaining genome stability in eukaryotes with a focus on the yeast model organism.

Keywords: reactive oxygen species;DNA damage response;damage checkpoint signaling;genome stability

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Functional interplay between the oxidative stress response and DNA damage checkpoint signaling for genome maintenance in aerobic organisms

J. Microbiol. 2020;58(2):81-91. Published online December 23, 2019

DOI: https://doi.org/10.1007/s12275-020-9520-x

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